Telomeric expression sites are highly conserved in Trypanosoma brucei.
Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.
Hertz-Fowler
Christiane
C
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom. chf@sanger.ac.uk
Figueiredo
Luisa M
LM
Quail
Michael A
MA
Becker
Marion
M
Jackson
Andrew
A
Bason
Nathalie
N
Brooks
Karen
K
Churcher
Carol
C
Fahkro
Samah
S
Goodhead
Ian
I
Heath
Paul
P
Kartvelishvili
Magdalena
M
Mungall
Karen
K
Harris
David
D
Hauser
Heidi
H
Sanders
Mandy
M
Saunders
David
D
Seeger
Kathy
K
Sharp
Sarah
S
Taylor
Jesse E
JE
Walker
Danielle
D
White
Brian
B
Young
Rosanna
R
Cross
George A M
GA
Rudenko
Gloria
G
Barry
J David
JD
Louis
Edward J
EJ
Berriman
Matthew
M
D000818:Animals; D000940:Antigenic Variation / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006790:Host-Parasite Interactions / Q000235:genetics; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016324:Sequence Tagged Sites; D016615:Telomere / Q000235:genetics*; D024363:Transcription Initiation Site / Q000502:physiology*; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000502:physiology